ArticleJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology2021
Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples.
Article in Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 73 citations in OpenAlex.
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- Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings.PloS one · 2026Article
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- VirNucPro: an identifier for the identification of viral short sequences using six-frame translation and large language models.Briefings in bioinformatics · 2025Article
- Safety and Diagnostic Utility of Brain Biopsy and Metagenomics in Decision-Making for Patients with Inborn Errors of Immunity (IEI) and Unexplained Neurological Manifestations.Journal of clinical immunology · 2025Article
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- Anellovirus abundance as an indicator for viral metagenomic classifier utility in plasma samples.Virology journal · 2025Article
- Leveraging innovative diagnostics as a tool to contain superbugs.Antonie van Leeuwenhoek · 2025Review
- AI-powered analysis of viral metagenomic sequencing data for rapid outbreak investigation and novel pathogen discovery.Frontiers in microbiology · 2025Review
- Exploring the Spectrum of Microbiota in Central Nervous System Infections Through Metagenomic Next-Generation Sequencing.Infection and drug resistance · 2025Article
- Accessible viral metagenomics for public health and clinical domains with Jovian.Scientific reports · 2024Article
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Authors and funding
30 authors at 16 institutions in 11 countries.
Funding
Abstract
introductionMetagenomic sequencing is increasingly being used in clinical settings for difficult to diagnose cases. The performance of viral metagenomic protocols relies to a large extent on the bioinformatic analysis. In this study, the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS) initiated a benchmark of metagenomic pipelines currently used in clinical virological laboratories.
methodsMetagenomic datasets from 13 clinical samples from patients with encephalitis or viral respiratory infections characterized by PCR were selected. The datasets were analyzed with 13 different pipelines currently used in virological diagnostic laboratories of participating ENNGS members. The pipelines and classification tools were: Centrifuge, DAMIAN, DIAMOND, DNASTAR, FEVIR, Genome Detective, Jovian, MetaMIC, MetaMix, One Codex, RIEMS, VirMet, and Taxonomer. Performance, characteristics, clinical use, and user-friendliness of these pipelines were analyzed.
resultsOverall, viral pathogens with high loads were detected by all the evaluated metagenomic pipelines. In contrast, lower abundance pathogens and mixed infections were only detected by 3/13 pipelines, namely DNASTAR, FEVIR, and MetaMix. Overall sensitivity ranged from 80% (10/13) to 100% (13/13 datasets). Overall positive predictive value ranged from 71-100%. The majority of the pipelines classified sequences based on nucleotide similarity (8/13), only a minority used amino acid similarity, and 6 of the 13 pipelines assembled sequences de novo. No clear differences in performance were detected that correlated with these classification approaches. Read counts of target viruses varied between the pipelines over a range of 2-3 log, indicating differences in limit of detection.
conclusionA wide variety of viral metagenomic pipelines is currently used in the participating clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implicating the need for standardization and validation of metagenomic analysis for clinical diagnostic use. Future studies should address the selective effects due to the choice of different reference viral databases.
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